Condition category
Circulatory System
Date applied
07/09/2020
Date assigned
14/09/2020
Last edited
14/09/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Venous leg ulcers are common, recurring open wounds on the lower leg. Compression is the first line of treatment for venous leg ulcers. A range of compression therapies such as four-layer bandages two-layer hosiery, two-layer bandages and compression wraps are regularly used in the NHS. However, we are unsure whether one compression therapy is more effective at treating venous leg ulcers than the others. Therefore, this study will aim to investigate the clinical and cost-effectiveness of compression therapies for treating venous leg ulcers.

Who can participate?
Adults with a venous leg ulcer

What does the study involve?
Following obtaining consent, eligible participants will be asked to complete a baseline questionnaire asking about their health and ulcer(s) and have a photo taken of their reference ulcer (as determined by the recruiting healthcare professional). Participants will then be randomly allocated to one of three treatment groups:
1. Compression wraps (adjustable hook-and-loop-fastened compression): A compression sleeve around the foot and leg
2. Evidence based compression (Four-layer bandage or two-layer compression hosiery):The participant and their healthcare professional will decide which treatment they receive. This will be either four layers of compression bandages or two layers of compression stockings
3. Two-layer compression bandage: This bandage will comprise of an initial bandage layer with a top compression bandage

Participants will then continue to see their healthcare professional for routine ulcer treatments to be carried out as normal. The healthcare professional will check how the ulcer is healing and record details of any changes to their treatment. Clinical events such as reference leg healing, ulcer recurrence, amputation, admission and discharge or death will also be recorded if and when they occur.

Once the participant’s ulcer has healed, a photograph of the reference ulcer will be taken once a week for 4 weeks. Following the healing of the leg ulcer, a nurse will also contact the participant once a month, by telephone, to check that the ulcer has not returned.

Whichever treatment a participant receives, they will be asked to complete a questionnaire booklet at 1, 3, 6, and 12 months, asking about their health and ulcer(s). These questionnaires will be sent in the post with a prepaid envelope for their return. A £10 voucher will also be sent to participants at 12 months to thank them for their time.

At the end of the study, participants will return to standard NHS care with their treatment nurse or doctor. If their ulcer does not fully heal during the study the participant’s care will continue with the treatment their doctor or nurse feels is best.

What are the possible benefits and risks of participating?
Every effort will be made to improve a participant’s venous leg ulcers; however, we cannot say whether the ulcer will improve more quickly because of participation in the study. The information we get from this study may have a significant impact upon helping people and healthcare professionals make more informed treatment choices in the future.

Side effects for compression wraps, the two-layer bandage, four-layer bandages and the two-layer hosiery are uncommon and are treatments routinely used in the NHS for patients with venous leg ulcers. There are no anticipated increased risks through participation in this study. Being in the study will not harm or disadvantage your care in any way. Throughout the study, participants will continue to see their health care professional for wound treatments to be carried out as normal.

Where is the study run from?
The study is run from York Trials Unit, University of York (UK) and 16 NHS trusts (UK)

When is the study starting and how long is it expected to run for?
From February 2020 to January 2024

Who is funding the study?
The National Institute for Health Research Health Technology Assessment Programme (Project Number: NIHR128625) (UK)

Who is the main contact?
1. Miss Katherine Jones (public contact)
Katherine.jones@york.ac.uk
2. Dr Catherine Arundel (scientific contact)
Catherine.arundel@york.ac.uk

Trial website

www.york.ac.uk/healthsciences/research/trials/research/trials/venus6/

Contact information

Type

Public

Primary contact

Miss Katherine Jones

ORCID ID

Contact details

York Trials Unit
Department of Health Sciences - Faculty of Science
ARRC Building
University of York
Seebohm Rowntree Building
Heslington
York
YO10 5DD
United Kingdom
+44 (0)1904 321620
Katherine.jones@york.ac.uk

Type

Scientific

Additional contact

Dr Catherine Arundel

ORCID ID

Contact details

York Trials Unit
Department of Health Sciences - Faculty of Science
ARRC Building
University of York
York
YO10 5DD
United Kingdom
+44 (0)1904 321 116
Catherine.arundel@york.ac.uk

Type

Scientific

Additional contact

Prof Jo Dumville

ORCID ID

http://orcid.org/0000-0002-6546-3685

Contact details

The University of Manchester
Room 5.318
Jean McFarlane Building
Oxford Road
Manchester
M13 9PL
United Kingdom
+44 (0)161 306 7830
Jo.dumville@manchester.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 46547, IRAS 280987

Study information

Scientific title

A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6)

Acronym

VenUS 6

Study hypothesis

1. To compare compression wraps with evidence-based compression in terms of the time to healing of venous leg ulcers;
2. To determine whether two-layer bandages are non-inferior to evidence-based compression for time to healing of venous leg ulcers;
3. To determine which is the most cost-effective, full compression treatment for venous leg ulcers

Ethics approval

Pending, West of Scotland REC 4 (Ward 11, Dykebar Hospital, Grahamston Road, Paisley, PA2 7DE; +44 (0)141 314 0213; WoSREC4@ggc.scot.nhs.uk), ref: 20-WS-0121

Study design

Multi-centre, three-arm, parallel group, pragmatic randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Venous ulcers

Intervention

The study has a 32-month recruitment period, including an initial 6 month internal pilot. Follow-up will be variable with participants followed for minimum of 4 months and a maximum of 12 months.

Prior to study involvement the clinical care team will screen clinical caseloads at trial sites will assess participants against the eligibility criteria. Patients who may be eligible to participate in the study will be approached by a member of the research team and provided with a patient information sheet and asked to indicate if they would be interested in participating. Patients will be given sufficient time to consider this information.

Once eligibility has been confirmed, patients must take part in the consent process. During the consent process, the person obtaining consent will inform the participant of all aspects of the trial (e.g. trial procedures, risks/benefits) in order to allow the participant to make an informed decision about their participation. No protocol specific procedures are performed until the participant has signed and dated an Ethics Committee approved informed consent form.

Once informed consent has been obtained, baseline data will be collected and participants then randomised.

At baseline participant contact details, GP contact details, diabetes status, weight, height and general mobility and ankle mobility will be determined. Ulcer history and assessment such as duration and area of the reference ulcer, number of previous ulcer episodes, ankle–brachial pressure index and ankle circumference. A photo of the reference ulcer (where a participant has multiple ulcers the reference ulcer will be defined as that with the largest surface area) will be taken in order to monitor healing.

Following collection of baseline data, the research team will contact the UKCRC-accredited University of York Trials Unit (YTU) via the internet to access a secure randomisation service, which will ensure complete allocation concealment. The randomisation service will record information and check eligibility to avoid inappropriate entry of patients into the trial. Randomisation will be stratified by ulcer duration (<6 months and > 6 months) and ulcer area (< 5cm2 and > 5cm2) using permuted blocks; these variables are known predictors of healing. Participants will be randomly allocated 1:1:1 to either:
1. Arm 1: compression wraps
2. Arm 2: evidence based compression treatment (choice between four layer bandage or two layer compression hosiery)
3. Arm 3: two layer bandage Randomisation will be stratified by ulcer duration (<6 months and >6 months) and ulcer area (<5m2 and >5cm2) using permuted blocks
Once randomised, participants will begin their trial treatment as soon as it is available in line with what would happen in routine practice.

Participants will continue to receive standard care, including wound dressing changes, as per routine clinical practice. Study data on treatment use and clinical outcomes will be collected weekly during this period by the treatment team. This will include:
1. Healing of the reference ulcer. Treating nurses will be asked to report the date when they consider the reference ulcer and the reference leg has healed. Additionally, data on the reference ulcer will be collected throughout the study in the form of digital images. A digital image will be taken at baseline and again when the treating nurse records the reference ulcer as healed. After this point images will be taken once a week over the next 4 weeks. These images will be assessed by two blinded clinical experts to confirm the date of healing, with disagreements being resolved through discussion and the involvement of a third reviewer if required.
2. Treatments-received (including changes to trial treatment). treatments received will be logged every wound-related nurse visit to the participant, using a case report form, until either the participant’s reference leg (the leg with the reference ulcer on) is ulcer-free and no more nurse visits are required to treat this leg or until the participant exits the trial. The date of visit, the type of compression being received, and the type of primary contact dressing being used will be recorded. These resource use data will be used in economic analyses. If a participant changes from their allocated compression treatment, the date of this change, what they changed to, and the reason for this change; including whether the change from trial treatment was requested by the patient or based on a clinical decision, will b recorded.
3. Healing of the reference leg. Although the clinical analysis defined the primary outcome based on healing of the reference ulcer, the clinically relevant outcome is healing of all ulcers (ulcer free patient). It will be assumed that the reference leg is independent of the non-reference leg (even if this has ulcers), and that healing of the reference leg is the main outcome for evaluation in the economic analysis.
4. Recurrence. Following healing of the reference leg, monthly telephone assessment for ulcer recurrence will take place until the participant exits the trial. The maximum period for trial follow-up will be 12 months following randomisation, although due to variable follow-up some participants will be followed for less time (minimum 4 months).
5. Health related quality of life assessed using the VEnous INsufficiency Epidemiological and Economic Study - Quality of Life (VEINES-QOL) and the EuroQol 5-dimension 5-level quality of life questionnaire (EQ-5D-5L) at baseline, and at 1, 3, 6, and 12 months follow up (sent and returned via post)
6. Ulcer-related pain will be measured using the Visual Analogue Pain Scale (VAS) at baseline, and at 1, 3, 6, and 12 months follow up (sent and returned via post)
7. Resource use will be determined through a set of questions recording the ulcer-related care from the NHS within the past 3 months at 3, 6 and 12 months (sent and returned via post)
8. Participant adherence and ease of treatment use will be determined through a set of questions assessing views on the compression treatments, volume of treatment use and reasons for reduced dose at 1, 3, 6 and 12 months (sent and returned via post)

After the final assessment, participants will return to usual NHS care.

Two studies within a trial (SWATs) are planned to assess the effectiveness for methods to improve recruitment and retention:
1. Recruitment SWAT: Evaluation of the effects of presentation of the study design to participants on recruitment rate. Participants will be randomised to receive an infographic (visual document explaining the study) plus the standard patient information sheet (PIS) or just the PIS.
2. Retention SWAT: A 2 by 2 factorial design to simultaneously evaluate the effect of two retention strategies: a participant newsletter and a thank you card sent in advance of follow up questionnaires. Participants will be randomised to receive either: a newsletter and thank you card; a newsletter only; a thank you card only; or neither the newsletter nor the thank you card. These will be sent at Month 4 and Month 9 following randomisation to the VenUS 6 trial.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Time to healing of the reference ulcer, defined as 'complete epithelial cover in the absence of a scab with no dressing required. This will be measured by blinded assessment (by two independent blinded assessors, and where there is any disagreement in review, a third review may be completed) of digital images taken at baseline and when the treating nurse regards the reference ulcer as healed

Secondary outcome measures

1. Health-related quality of life measured using the VEnous INsufficiency Epidemiological and Economic Study - Quality of Life (VEINES-QOL) and the EuroQol 5-dimension 5-level quality of life questionnaire (EQ-5D-5L) at baseline, 1, 3, 6, and 12 months
2. Resource use measured using a set of questions recording the ulcer-related care from the NHS within the past 3 months at 3, 6, and 12 months
3. Wound-related pain measured using the Visual Analogue Pain Scale (VAS) at baseline, 1, 3, 6, and 12 months
4. Participant adherence and ease of treatment use measured using a set of questions assessing views on the compression treatments, volume of treatment use, and reasons for reduced dose at 1, 3, 6 and 12 months
5. Incidence of clinical events such as reference leg healing, ulcer recurrence, amputation, admission, and discharge or death will also be recorded if and when they occur

Overall trial start date

01/02/2020

Overall trial end date

31/01/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. ≥1 venous leg ulcer.
2. Ankle:brachial pressure index (ABPI) ≥0. 8 (taken within the previous 3 months or where an ABPI is not viable, use of locally-approved alternative assessments to rule out peripheral arterial disease i.e. pulse palpation and doppler ausculation toe pressure assessment or arterial imaging also taken within the last 3 months)
3. Able to tolerate full compression
4. Aged ≥18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 675; UK Sample Size: 675

Participant exclusion criteria

1. Unwilling to wear full compression
2. Leg ulcers of non-venous aetiology (e.g. arterial or rheumatoid)
3. significant peripheral vascular disease which contraindicates full compression ( requiring an APBI of at least 0.8)
4. Ulcers confined to the foot
5. Lacks capacity or willingness to provide consent to participate in the trial
6. Currently participating in another study evaluating treatments for their venous leg ulcer
7. Known allergy to any trial product
8. Previously recruited for this trial
9. Deemed to be not clinically appropriate to take part in the trial (at clinician discretion)
10. On a waiting list for endovenous ablation and is expected to have surgery within 28 days

Recruitment start date

01/10/2020

Recruitment end date

31/03/2023

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Manchester University NHS Foundation Trust
Cobbett House Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Leeds Community Healthcare NHS Trust
Stockdale House 8 Victoria Road
Leeds
LS6 1PF
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
Bradford Royal Infirmary Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Kent Community Health NHS Foundation Trust
Unit D The Oast Hermitage Lane
Maidstone
ME16 9NT
United Kingdom

Trial participating centre

Lancashire & South Cumbria NHS Foundation Trust
Sceptre Point Sceptre Way Bamber Bridge
Preston
PR5 6AW
United Kingdom

Trial participating centre

Northumbria Healthcare NHS Foundation Trust
North Tyneside General Hospital Rake Lane
North Shields
NE29 8NH
United Kingdom

Trial participating centre

Humber Teaching NHS Foundation Trust
Trust Hq, Willerby Hill Beverley Road Willerby
Hull
HU10 6ED
United Kingdom

Trial participating centre

University hospitals birmingham NHS Foundation Trust
Queen Elizabeth Hospital Mindelsohn Way Edgbaston
Birmingham
B15 2GW
United Kingdom

Trial participating centre

Cambridgeshire And Peterborough NHS Foundation Trust
Elizabeth House, Fulbourn Hospital Fulbourn
Cambridge
CB21 5EF
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals NHS Foundation Trust
Northern General Hospital Herries Road
Sheffield
S5 7AU
United Kingdom

Trial participating centre

Hull University Teaching Hospitals NHS Trust
Hull Royal Infirmary Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

Mid Yorkshire Hospitals NHS Trust
Pinderfields Hospital Aberford Road
Wakefield
WF1 4DG
United Kingdom

Trial participating centre

East Suffolk And North Essex NHS Foundation Trust
Colchester District General Hospital Turner Road
Colchester
CO4 5JL
United Kingdom

Trial participating centre

Cambridgeshire Community Services NHS Trust
Unit 7/8 Meadow Park Meadow Lane
St. Ives
PE27 4LG
United Kingdom

Trial participating centre

Norfolk Community Health And Care NHS Trust
Norwich Community Hospital Bowthorpe Road
Norwich
NR2 3TU
United Kingdom

Trial participating centre

Derbyshire Community Health Services NHS Foundation Trust
Trust Hq, Ash Green Disability Centre Ashgate Road Ashgate
Chesterfield
S42 7JE
United Kingdom

Sponsor information

Organisation

Manchester University NHS Foundation Trust

Sponsor details

Cobbett House
Oxford Road
Manchester
M13 9WL
United Kingdom
+44 (0)1612763432
research.sponsor@mft.nhs.uk

Sponsor type

Hospital/treatment centre

Website

https://mft.nhs.uk/

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR128625

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute for Health Research (NIHR) (UK)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Results from this study will be written up and submitted to peer-reviewed journals, irrespective of the magnitude or direction of effect. A publications policy will be generated in advance to detail authorship, acknowledgements and review processes for any publications arising from the VenUS 6 trial.

The executive summary and copy of the trial report will be sent to the National Institute for Health and Care Excellence (NICE) and other relevant bodies, including Clinical Commissioning Groups, so that study findings can be translated into clinical practice nationally. We will also work with the relevant National Clinical Director in the Department of Health to help ensure the findings of the trial are considered when implementing policy and will work with the Speciality Advisory Committees (SAC) to incorporate the findings into the training curriculum for clinicians who will undertake treatment of venous leg ulcers.

A summary of the study report will be produced and made available to participants, members of our patient advisory group and relevant patient-focused websites. Service users involved in the VenUS 6 patient advisory group will be asked to actively participate in the generation of this to ensure the results are easily accessible to patients.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

31/01/2025

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

08/09/2020: Trial’s existence confirmed by the National Institute for Health Research (NIHR).